The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation.
The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation.
复制标题
DOI：
10.1038/s41467-021-22639-6
复制
发表时间：
2021-05-11
影响因子：
16.6
通讯作者：
Bell CG
中科院分区：
文献类型：
--
作者：
Acton RJ;Yuan W;Gao F;Xia Y;Bourne E;Wozniak E;Bell J;Lillycrop K;Wang J;Dennison E;Harvey NC;Mein CA;Spector TD;Hysi PG;Cooper C;Bell CG
表观基因组已被证明会随着年龄的增长而恶化，可能会影响与衰老相关的疾病。tRNA虽然仅产生于约46 kb（<0.002%基因组），但其是第二丰富的细胞转录物。tRNA还通过核心翻译和其他调节作用控制已知影响衰老的代谢过程。在这里，我们询问人类tRNA基因组位点的DNA甲基化状态。我们确定了一个基因组富集年龄相关的DNA超甲基化的tRNA位点。对4，350个MeDIP-seq外周血DNA甲基化组（16-82岁）的分析，分别在研究和全基因组显著性上鉴定出44个和21个高甲基化特异性tRNA，与无低甲基化形成对比。验证和复制（450 k阵列和独立靶向Bisuphite测序）支持该功能单元的超甲基化。组织特异性是一个重要的驱动因素，尽管最强的一致信号（也与主要细胞类型变化无关）发生在tRNA-iMet-CAT-1-4和tRNA-Ser-阿加-2-6中。这项研究提出了一个全面的评估人类tRNA基因的基因组DNA甲基化状态，并揭示了一个谨慎的超甲基化随着年龄的增长。表观基因组已被证明会随着年龄的增长而变化，可能会影响与年龄相关的疾病。在这里，作者研究了人类tRNA基因组位点的DNA甲基化状态，并观察到tRNA位点上与年龄相关的DNA超甲基化的富集。
The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16–82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with none hypomethylating. Validation and replication (450k array and independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age. The epigenome has been shown to change with age, potentially impacting on ageing-related disease. Here the authors investigate the DNA methylation state of the genomic loci of human tRNA and observe enrichment for age-related DNA hypermethylation at tRNA loci.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
12.3
作者：
Bell CG;Xia Y;Yuan W;Gao F;Ward K;Roos L;Mangino M;Hysi PG;Bell J;Wang J;Spector TD
通讯作者：
Spector TD
影响因子：
14.9
作者：
Darrow EM;Chadwick BP
通讯作者：
Chadwick BP
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M